Numerous diseases of humans and animals are caused by microorganisms that colonize the internal nasal passages and the alimentary tract, which comprises the mouth, pharynx, and gastrointestinal tract. While many of these diseases are acute conditions caused by bacteria that are self-limiting or treatable by conventional antibiotic therapy, others are caused by microorganisms that tend to establish chronic infections that cause continuing symptoms and are often difficult to treat with antibiotics.
Gastritis and duodenal peptic ulcers (commonly described as peptic ulcer disease) involve an inflammation and/or erosion of the mucosal lining of the stomach or duodenum. These pathological conditions were thought for many years to be the result of hypersecretion of stomach acid caused by either genetic predisposition, stress, or diet, or a combination of these factors. This belief led to a medical treatment regime including drugs of various classes (antacids, histamine H2 receptor antagonists, H+ inhibitors, K+ inhibitors, proton pump inhibitors, ATPase inhibitors and the like) that neutralize the excess acid or inhibit its secretion. While such therapy has had generally good results, it is often necessary to continue the treatment for the patient's entire lifespan because discontinuing treatment usually results in relapse of the disease. Recently, it has been established that the pathogen Helicobacter pylori, a spiral bacterium, is a factor in the development of gastritis and duodenal peptic ulcers. This bacterium has been found to colonize the gastric epithelium and to cause damage to the epithelial cells which results in a gastritis that predisposes the organ to the formation of ulcers. H. pylori has also been linked to development of gastric adenocarcinoma and B cell lymphoma in the stomach. H. pylori's in vivo role in gastritis and peptic ulcers and its association with the second leading cause of cancer deaths in the world, gastric cancer (second only to lung cancer), make it one of the world's most prevalent and significant pathogens.
Indeed, in recent years it has come to be recognized that H. pylori infection of the stomach can result in a broad spectrum of debilitating disease outcomes, including gastritis, non-ulcer dyspepsia, peptic ulcer disease, and gastric cancers. For example, in the United States about 50% of the population may be infected with this organism, and currently about 25 million patients suffer from peptic ulcer disease. Each year there are 500,000 to 850,000 new cases and more than one million ulcer-related hospitalizations. On a global scale, the frequency of H. pylori infection is much higher and kills 7 million people each year.
In recent years, treatment of H. pylori infection with antimicrobial therapy has been found to heal peptic ulcers, eliminate chronic gastritis and dyspepsia, and may lead to regression of gastric cancer. However, there is currently no therapy that is 100% effective. Although numerous antibiotics have activity against H. pylori in vitro, therapy with a single antibiotic is generally ineffective in clinical practice. Successful treatment often requires combination therapy consisting of 3-4 drugs given for periods of 10-14 days. Treatment failure occurs frequently, and second-line treatments with new antibiotic regimens are common. Perhaps the single most important factor influencing treatment is the emergence of antibiotic-resistant strains of H. pylori. Consequently, antibiotic therapy may be subject to certain limitations in the future.
Cryptosporidium parvum is a pathogenic intestinal protozoan with worldwide distribution that is a frequent cause of both endemic and epidemic diarrheal illness. This illness is particularly devastating in immunocompromised individuals, producing diarrhea with profuse watery stools accompanied by cramping, abdominal pain, nausea, vomiting, malaise and low grade fever that increases over months and years. Currently, there are no preventative therapies and anti-infective drugs are of limited efficacy.
Periodontal disease is a major reason for tooth loss in adults. Microbioloyically, periodontal disease is a polymicrobic problem involving anaerobic bacteria: Treponema denticola, Bacteroides forsythus, Actinobacillus actinomycetemcomitans, Campylobacter rectus, Prevotella intermedia, and Porphyromonas gingivalis, as well as others. This disease is more prominent in patients with dental implants, since the natural gum never fully adheres to the implant (false tooth) providing space for bacterial attachment and growth. Currently, treatments include more frequent tooth cleaning by dental hygienists, more frequent brushing with special dentifrices, and more frequent use of mouthwashes. While all current treatments decrease the probability and severity of periodontal disease, there is still a significant amount of tooth loss and none of the current approaches deals effectively with microbial attachment to the tooth or the buccal mucosa (gum).
Streptococcus pyogenes is an organism that can cause an acute pharyngitis with suppurative consequences caused by spread to other organs (otitis media, abscesses, meningitis, and the like) and/or non-suppurative consequences caused by toxins produced by some strains (scarlet fever). It is generally controllable with penicillins, but other methods of treatment are desirable because allergic reactions to penicillin are not uncommon.
Accordingly, a need has continued to exist for improved methods of treating and preventing disease of the oral cavity and alimentary tract caused by pathogenic microorganisms. In particular, a need has continued to exist for safe and effective methods of treating gastro-intestinal disorders due to infection with H. pylori. 